OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

OBJECTIVE: To explore the genetic basis of a patient with clinically suspected Loeys-Dietz syndrome (LDS). METHODS: A child who had presented at Beijing Anzhen Hospital in September 2018 was selected as the study subject. Clinical data and family history of the patient were collected, along with peripheral blood samples of the proband and his parents. Whole exome sequencing (WES) was carried out through next-generation sequencing. RESULTS: Candidate variants were searched through bioinformatic analysis focusing on genes associated with hereditary aortic aneurysms. Candidate variant was verified by Sanger sequencing. The patient was found to have cardiovascular abnormalities including early-onset aortic dilatation and coarctation, and LDS syndrome was suspected. WES revealed that he has harbored a heterozygous c.1526G>T missense variant of the TGFBR2 gene. The same variant was not found in either parent and was predicted as likely pathogenic (PM1+PM2_Supporting+ PM6+PP3+PP4) based on the guidelines from the American College for Medical Genetics and Genomics (ACMG). CONCLUSION The TGFBR2 c.1526G>T variant probably underlay the LDS in this patient and was unreported previously in China. Above finding has enriched the mutational spectrum of the TGFBR2 gene associated with the LDS and provided a basis for the genetic counseling for the patient.
Child ; Humans ; Male ; China ; Computational Biology ; Family ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Receptor, Transforming Growth Factor-beta Type II/genetics*

Aneurysm, Dissecting/complications* ; Coronary Artery Disease/complications* ; Dyspnea/complications* ; Humans ; Syncope/etiology*

Objective: To investigate the prognosis factors for death within 90 days after discharge in patients with acute kidney injury(AKI) treated requiring continuous renal replacement therapy(CRRT) undergoing surgery for acute Standford type A aortic dissection. Methods: The clinic data of 126 patients undergoing CRRT for postoperative AKI after acute type A aortic dissection surgery in the Center for Cardiac Intensive Care, Beijing Anzhen Hospital from July 2016 to February 2019 were analyzed retrospectively. There were 83 males and 43 females, aging (52.9±11.2) years(range: 25 to 70 years). The patients' demographic characteristics, disease-related information, perioperative data, laboratory indexes during CRRT, complications, and survival information within 90 days after discharge were recorded. Independent prognosis factors for death within 90 days of discharge were determined by Kaplan-Meier survival analysis, univariate and multifactorial Cox regression analysis. Results: Totally 57 of 126 patients(45.2%) died over the first 90 days after discharge. Kaplan-Meier survival analysis and univariate Cox regression analysis showed that there were significant differences between the non-survival and survival group including ≥65 years old, high lactate values 12 hours after CRRT, pulmonary infection, liver dysfunction, presence of permanent neurological complications, and postoperative ejection fraction(EF)<45%. Multifactorial Cox regression analysis revealed that ≥65 years old(HR=2.14, 95%CI: 1.09 to 4.21, P=0.03), high lactate values 12 hours after CRRT(HR=1.13, 95%CI: 1.06 to 1.20, P=0.01) and postoperative EF<45%(HR=2.21, 95%CI: 1.09 to 4.51, P=0.03) were independent prognosis factors for patients' death within 90 days after hospital discharge. Conclusions: ≥65 years old, high lactate values 12 hours after CRRT and postoperative EF<45% are independent prognosis factors for death within 90 days after discharge in patients undergoing CRRT for AKI after acute type A aortic dissection surgery. Proper identification and management of prognosis factors could be beneficial to improve patients' outcomes.
Acute Kidney Injury/therapy* ; Aged ; Aneurysm, Dissecting/surgery* ; Continuous Renal Replacement Therapy ; Female ; Humans ; Lactates ; Male ; Patient Discharge ; Prognosis ; Renal Replacement Therapy/adverse effects* ; Retrospective Studies ; Risk Factors

Carotid arterial dissections may result from spontaneous or traumatic causes. Postcoital arterial dissections have been reported in both the vertebral and coronary arteries. We report a rare case of spontaneous dissection on the extracranial internal carotid artery in a Filipino female after sexual intercourse, leading to a fulminant middle cerebral artery (MCA) territory infarct. Although postcoital carotid artery dissection is a very rare cause of neck vessel dissections, its rapid progressive course can lead to massive cerebral infarction and prompt management must be initiated.
Cerebral Infarction ; Carotid Artery, Internal, Dissection

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun's operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.
Aneurysm, Dissecting/surgery* ; Humans ; Hypertension ; Male ; Postoperative Period ; Risk Factors ; Sleep Apnea, Obstructive

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10
Aneurysm, Dissecting/genetics* ; Case-Control Studies ; Cluster Analysis ; Cohort Studies ; Collagen Type III/genetics* ; Computational Biology ; Genetic Predisposition to Disease ; Humans

Acute Disease ; Aneurysm, Dissecting/therapy* ; Aortic Aneurysm/complications* ; China ; Consensus ; Coronary Angiography ; Coronary Artery Disease/therapy* ; Humans

OBJECTIVE: To explore the genetic basis for a patient with aortic root aneurysm and valve insufficiency. METHODS: The patient was subjected to whole exome sequencing (WES) with a focus on the analysis of genes related to aortic aneurysm and other genetic diseases involving the cardiovascular system. Suspected pathogenic site was validated by Sanger sequencing of the patient and his family members. RESULTS: WES has revealed a heterozygous c.830T>C variant (NM_001130916.3) in the patient, which was not detected among healthy members of his family. SIFT, PolyPhen2 and Mutation Taster predicted the variant to be disease causing, resulting in destruction of the structure and function of the TGFBR1 protein. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM1+PM2+PM6+PP3+PP4). CONCLUSION The c.830T>C variant of the TGFBR1 gene probably underlay the disease in the proband. Above finding has enriched the spectrum of TGFBR1 gene variants in Chinese population.
China ; Echocardiography ; Humans ; Loeys-Dietz Syndrome/genetics* ; Mutation ; Pedigree ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Whole Exome Sequencing

Aneurysm, Dissecting/surgery* ; Aorta, Thoracic/surgery* ; Aortic Aneurysm, Thoracic/surgery* ; Blood Vessel Prosthesis Implantation ; Dissection ; Humans ; Treatment Outcome